Pharmaceutisch Weekblad

, Volume 9, Supplement 1, pp S33–S40 | Cite as

Influence of dose frequency on the therapeutic efficacies of ciprofloxacin and ceftazidime in experimental Klebsiella pneumoniae pneumonia and septicemia in relation to their bactericidal activities in vitro

  • R. Roosendaal
  • I. A. J. M. Bakker-Woudenberg
  • M. van Den Berghe-Van Raffe
  • J. C. Vink-Van Den Berg
  • M. F. Michel


The antibacterial activities of ciprofloxacin versus ceftazidime againstKlebsiella pneumoniae in vitro andin vivo were compared. Although there was only a minor difference in MBC values between both drugs ciprofloxacin demonstrated a high and dose-dependent bacterial killing ratein vitro and in lungs of leukopenic rats in contrast to the more time-dependent bactericidal activity of ceftazidime. After treatment of aK.pneumoniae pneumonia and septicemia the efficacy of ciprofloxacin was only slightly influenced by the mode of administration, either at 6-h intervals or continuously, whereas ceftazidime was far more effective after continuous administration. This resulted in a superior efficacy of ciprofloxacin after intermittent treatment as compared to ceftazidime, whereas ceftazidime was more effective after continuous administration as compared to ciprofloxacin. Also ciprofloxacin proved to be bactericidal against bacteria that were not actively growing, bothin vitro andin vivo, whereas ceftazidime was not.

Key words

Antibiotic dose schedule Ceftazidime Ciprofloxacin Klebsiella pneumoniae 


  1. 1.
    Klastersky J, Glauser MP, Schimpff SC, Zinner SH, Gaya H, and The European Organization for Research on Treatment of Cancer antimicrobial therapy project group. Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients. Antimicrob Agents Chemother 1986;29:263–70.PubMedGoogle Scholar
  2. 2.
    Kramer BS, Pizzo PA, Robichaud KJ, Witesbsky F, Wesley R. Role of serial microbiologic surveillance and clinical evaluation in the management of cancer patients with fever and granulocytopenia. Am J Med 1982;72:561–8.PubMedGoogle Scholar
  3. 3.
    Sculier JP, Weerts D, Klastersky J. Causes of death in febrile granulocytopenic cancer patients receiving empiric antibiotic therapy. Eur J Cancer Clin Oncol 1984;20:55–60.PubMedGoogle Scholar
  4. 4.
    Chalkley LJ, Koomhof HJ. Antimicrobial activity of ciprofloxacin againstPseudomonas aeruginosa, Escherichia coli, andStaphylococcus aureus determined by the killing curve method: Antibiotic comparisons and synergistic interactions. Antimicrob Agents Chemother 1985;28:331–42.PubMedGoogle Scholar
  5. 5.
    Zeiler HJ. Evaluation of the in vitro bactericidal action of ciprofloxacin on cells ofEscherichia coli in the logarithmic and stationary phase of growth. Antimicrob Agents Chemother 1985:28:524–7.PubMedGoogle Scholar
  6. 6.
    Cozens RM, Tuomanen E, Tosh W, Zak O, Suter J, Tomasz A. Evaluation of the bactericidal activity of ß-lactam antibiotics on slowly growing bacteria cultured in the chemostat. Antimicrob Agents Chemother 1986;29:797–802.PubMedGoogle Scholar
  7. 7.
    Bakker-Woudenberg IAJM, van den Berg JC, Michel MF. Therapeutic activities of cefazolin, cefotaxime, and ceftazidime against experimentally inducedKlebsiella pneumaniae pneumonia in rats. Antimicrob Agents Chemother 1982;22:1042–50.PubMedGoogle Scholar
  8. 8.
    Thonus IP, de Lange-Macdaniel AV, Otte CJ, Michel MF. Tissue cage infusion: a technique for the achievement of prolonged steady stage in experimental animals. J Pharmacol Methods 1979;2:63–9.Google Scholar
  9. 9.
    Sachs L. Evaluation of biologically active substances based on dosage — dichotomous effect curves. In: Sachs L, ed. Applied statistics. A handbook of techniques. New York: Springer Verlag, 1982;224–8.Google Scholar
  10. 10.
    Bennett JV, Brodie JL, Benner EJ, Kirby WMM. Simplified accurate method for antibiotic assay of clinical specimens. Appl Microbiol 1966;14:170–7.PubMedGoogle Scholar
  11. 11.
    Bakker-Woudenberg IAJM, Berg van den JC, Vree TB, Baars AM, Michel MF. Relevance of serum protein binding of cefoxitin and cefazolin to their activities againstKlebsiella pneumoniae pneumonia rats. Antimicrob Agents Chemother 1985:28:654–9.PubMedGoogle Scholar
  12. 12.
    Bergogne-Berezin E, Berthelot G, Even P, Stern M, Reynaud P. Penetration of ciprofloxacin into bronchial secretions. Eur. J Clin Microbiol 1986:5:197–200.PubMedGoogle Scholar
  13. 13.
    Hooper DC, Wolfson JS. The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother 1985:28:716–21.PubMedGoogle Scholar
  14. 14.
    Nichol KL, Peterson, Fasching CE, Gerding DN. Ciprofloxacin penetration into extravascular spaces in a rabbit model. Antimicrob Agents Chemother 1984:26:935–6.PubMedGoogle Scholar
  15. 15.
    Wise R, Lockley RM, Webberly M, Dent J. Pharmacokinetics of intravenously administered ciprofloxacin. Antimicrob Agents Chemother 1984:26:208–10.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1987

Authors and Affiliations

  • R. Roosendaal
    • 1
  • I. A. J. M. Bakker-Woudenberg
    • 1
  • M. van Den Berghe-Van Raffe
    • 1
  • J. C. Vink-Van Den Berg
    • 1
  • M. F. Michel
    • 1
  1. 1.Department of Clinical Microbiology and Antimicrobial TherapyErasmus University RotterdamDR RotterdamThe Netherlands

Personalised recommendations